Marek Mori

Individual variability in the diurnal intraocular pressure curve.

BACKGROUND Reduction of intraocular pressure (IOP) is a primary goal of most glaucoma treatments. However, because the IOP varies during the day, single measurements performed in an ophthalmologists office do not necessarily provide information on the peak level and fluctuation of the IOP. METHODS Home tonometry was performed to gain more information on the nature of the diurnal IOP curves and on their variability. One hundred seventy-six patients with open-angle glaucoma (OAG), 55 subjects with ocular hypertension (OHT), and 18 control individuals measured their IOP five times daily at home for 4 to 8 consecutive days using a self-tonometer. RESULTS Well-defined diurnal IOP variations were observed in all three groups with a predominance of curves with morning or mid-day maxima. Erratic IOP curves without a diurnal rhythm were present in OHT (22%) and OAG (16%) patients but not in control subjects. Differences between the curves of the two eyes of an individual were frequent in OHT (33%) and OAG (36%) patients but not in control subjects (6%). Finally, the majority of OHT (72%) and OAG (66%) patients showed a difference in their diurnal curve patterns on repeat home tonometry performed months apart. CONCLUSION The authors indicate that it is difficult to rely on one eye as a control for the other. They also indicate that changes in IOP observed in the office at different visits often may be due to a shift in the type of diurnal curve rather than to a true change in the mean IOP. Monitoring of the diurnal IOP may be necessary in some cases if the clinician relies, even partially, on the level of IOP when making a decision on patient management.

Topography of the Retinal Thickness in Normal Subjects

A noninvasive method has been developed that is capable of providing quantitative thickness profiles of the retina. The method was used to map the retinal thickness in five normal human volunteers and determine the reproducibility of the measurements. The reproducibility or equivalent sensitivity of the measurements to detect changes was found to be 5% or 19 microns on the same day and 8% or 31 microns on different days. By averaging the values obtained in five normal subjects, ranging in age from 21 to 43 years (mean, 34 years), a preliminary normal baseline was derived for the thickness profile at the fovea and the thickness cross-section from the optic disc to the fovea. The results of the study indicated that this noninvasive method promises to be of clinical use in diagnosing ocular diseases that produce changes in the thickness of the retinal as well as in monitoring the effectiveness of therapy.

A Method for Chorioretinal Oxygen Tension Measurement

Purpose: To report an optical imaging system that was developed to measure oxygen tension (pO2) in the chorioretinal vasculatures. The feasibility of the system for the measurement of changes in pO2 separately in the retinal and choroidal vasculatures was established in rat eyes by varying the fraction of inspired oxygen and inhibiting nitric oxide activity. Methods: Our optical section phosphorescence imaging system was modified to provide quantitative measurements of pO2 separately in the retinal and choroidal vasculatures. A narrow laser line was projected at an angle on the retina after intravenous injection of an oxygen-sensitive probe (Pd-porphyrin), and phosphorescence emission was imaged. A frequency-domain approach allowed measurements of the phosphorescence lifetime by varying the phase relationship between the modulated excitation laser light and sensitivity of the imaging camera. Chorioretinal pO2 was measured while varying the fraction of inspired oxygen and during intravenous infusion of Nω-nitro-L-arginine (Nω-NLA), a nonselective nitric oxide synthase inhibitor. Results: The systemic arterial pO2 varied according to the fraction of inspired oxygen. The pO2 in the retinal and choroidal vasculatures increased as the fraction of inspired oxygen was increased. Compared with baseline, choroidal pO2 decreased during infusion of Nω-NLA, whereas the pO2 in the retinal vasculatures remained relatively unchanged. The choroidal pO2 decreased markedly with each incremental increase in Nω-NLA infusion rate, in the range 1–6 mg/min, and there was no additional change in the choroidal pO2 at Nω-NLA infusion rates above 6 mg/min. Conclusions: An optical method combining pO2 phosphorescence imaging with chorioretinal optical sectioning was established that can potentially be applied for better understanding of retinal and choroidal oxygen dynamics in physiologic and pathologic states.

Three-dimensional mapping of chorioretinal vascular oxygen tension in the rat.

PURPOSE An optical section phosphorescence lifetime imaging system was developed for three-dimensional mapping of oxygen tension (P(O2)) in chorioretinal vasculatures. METHODS A laser line was projected at an oblique angle and scanned on the retina after intravenous injection of an oxygen-sensitive molecular probe to generate phosphorescence optical section images. An automated software algorithm segmented and combined images from spatially adjacent locations to construct depth-displaced en face retinal images. Intravascular P(O2) was measured by determining the phosphorescence lifetime. Three-dimensional chorioretinal P(O2) maps were generated in rat eyes under varying fractions of inspired oxygen. RESULTS Under an air-breathing condition, mean P(O2) in the choroid, retinal arteries, capillaries, and veins were 58+/-2 mm Hg, 47+/-2 mm Hg, 44+/-2 mm Hg, and 35+/-2 mm Hg, respectively. The mean arteriovenous P(O2) difference was 12+/-2 mm Hg. With a lower fraction of inspired oxygen, chorioretinal vascular P(O2) and mean arteriovenous P(O2) differences decreased compared with measurements under an air-breathing condition. Retinal venous P(O2) was statistically lower than P(O2) measured in the retinal artery, capillaries, and choroid (P<0.004). CONCLUSIONS Three-dimensional mapping of chorioretinal oxygen tension allowed quantitative P(O2) measurements in large retinal blood vessels and in retinal capillaries. This method has the potential to facilitate better understanding of retinal oxygenation in health and disease.

Clinical Assessment of the Macula by Retinal Topography and Thickness Mapping

PURPOSE To report a quantitative and objective method for assessing pathologic alterations in retinal structures to improve the evaluation of macular diseases. METHODS We used a system based on the scanning retinal thickness analyzer to generate serial optical section images of the retina and provide mapping of the retinal topography and thickness in a normal subject and in patients with representative maculopathies including traumatic macular hole, central serous chorioretinopathy, branch retinal vein occlusion, diabetic macular edema, and retinal pigment epithelial detachment. RESULTS The effectiveness of the system in imaging both the vitreoretinal and chorioretinal interfaces was confirmed in the normal subject and in patients with various maculopathies. Mapping of retinal topography and thickness in a normal eye correlated well with normal anatomy, delineating the foveal depression clearly. The retinal thickness map in a patient with diabetic macular edema showed thickening of the retina and absence of a foveal depression. The patients with central serous chorioretinopathy and branch retinal vein occlusion had an elevated vitreoretinal surface. Conversely, the patient with retinal pigment epithelial detachments had a relatively flat vitreoretinal interface but an irregularly elevated chorioretinal surface. CONCLUSION Quantitative mapping of retinal topography and thickness is a promising tool that may improve evaluation of macular diseases.

Enhanced Visualization of Vitreoretinal Interface by Laser Biomicroscopy

BACKGROUND The use of slit-lamp biomicroscopy provides valuable information for the diagnosis and management of vitreoretinal disorders. However, intense backscatter from the fundus often precludes the visualization of fine structures in the vitreoretinal interface. METHODS Laser biomicroscopy is a new method designed to improve the visualization of fine vitreoretinal structures at the macula. This method was applied to eyes suspected of traction maculopathies. With this method, the contrast and the lateral separation between the vitreal and retinal images are optimized while preserving information on the location of the slit on the fundus. RESULTS The results indicated that fine structures in the vitreoretinal interface, which were difficult to observe with conventional slit-lamp biomicroscopy, could be clearly visualized. CONCLUSION Laser biomicroscopy may be a useful tool in the diagnosis and management of diseases with vitreoretinal abnormalities.

Thickness of the peripapillary retina in healthy subjects with different degrees of ametropia

PURPOSE To evaluate the thickness of the peripapillary retina in healthy subjects with different degrees of ametropia. DESIGN Cross-sectional study. PARTICIPANTS Forty-three healthy normal subjects, ages 15 to 64 years (38+/-15 years) were recruited. METHODS The method of retinal thickness mapping was applied to generate serial optical section images in the temporal peripapillary retinal area. The digitized images were analyzed to detect the separation between the vitreoretinal and chorioretinal interfaces. The separation was converted to absolute thickness by taking into account the magnification of the optical system and the optical dimensions of the eyes. MAIN OUTCOME MEASURES The refractive error of the eyes ranged from +8.25 to -12.75 diopters (spherical equivalent). The axial length of the eyes ranged from 19.3 to 27.35 mm. The retinal thickness in a 2- x 2-mm temporal peripapillary retinal area was determined. RESULTS The separation between the retinal interfaces decreased with increasing axial length (P<0.001). The thickness in the temporal peripapillary retinal area was not significantly correlated with the axial length of the eye (P = 0.3). A lack of statistically significant difference between the average thickness in the hyperopic, emmetropic, and myopic eyes (P> or =0.06) was found. CONCLUSIONS The average thickness in the temporal peripapillary retinal area was not influenced by the axial length of the eye, when the magnification of the optical system and the optical dimension of the eyes were taken into consideration.

Optical section retinal imaging and wavefront sensing in diabetes.

Purpose. To investigate differences in higher-order ocular aberrations and in optical section retinal image resolution between healthy normal and diabetic subjects. Methods. An optical imaging system was established for combined retinal optical section imaging and wavefront sensing. A laser beam was expanded and focused to a point on the retina by the optics of the eye. For optical section retinal imaging, a cylindrical lens was placed in the path of the incident laser beam to form a focused line on the retina. Because of the angle between the incident laser and imaging path, an optical section image of the retina was captured. For wavefront sensing, a Shack-Hartmann aberrometer was incorporated in the imaging system. Twenty-two subjects with diabetes (average age, 52 ± 12 years) and 13 normal subjects (average age, 47 ± 9 years) were imaged. Retinal depth resolution was determined from the width of the laser line on the retina. Higher-order ocular aberrations were determined from the root mean square of the third to seventh Zernike terms, characterizing the wavefront aberration function. The data were analyzed statistically using Student’s t-test and linear regression. Results. Higher-order ocular aberrations in diabetic subjects were significantly higher than in normal subjects (p = 0.03). The retinal image depth resolution in diabetic subjects was significantly lower than in normal subjects (p < 0.001). The retinal image depth resolution was inversely correlated with higher-order aberrations (r = −0.5; p = 0.007; N = 35). Conclusions. The results demonstrate disease-related increases in higher-order ocular aberrations that influence retinal image resolution in diabetic eyes. This information is useful for designing high-resolution retinal imaging systems applicable for eyes with retinal disease.

Findings on retinal topography and thickness mapping in age-related macular degeneration.

Purpose To report alterations in the retinal topography and thickness in typical cases of age-related macular degeneration (ARMD). Methods An optical imaging system was applied to patients with ARMD with alterations in the retinal structures. The system generates a series of 20 optical section images that encompass a 2 mm × 2 mm retinal area. The optical sections are digitized and analyzed to provide topographic maps of the vitreo-retinal and chorio-retinal surfaces and the retinal thickness. Results Retinal topography and thickness mapping in a normal eye corresponded to normal anatomy. Topographic mapping in a patient with confluent drusen indicated elevation of the vitreo-retinal surface. Retinal topography in a patient with retinal pigment epithelium detachment displayed localized elevation of the chorio-retinal surface. The thickness map in a patient with geographic atrophy of the retinal pigment epithelium revealed retinal thinning. In the patients with choroidal neovascularization, the vitreo-retinal and chorio-retinal surfaces were elevated. The chorio-retinal surface map in a patient with evolving disciform scar displayed topographic variations corresponding to the fibrovascular tissue underlying the serous detachment. Conclusion Retinal topography and thickness mapping is useful for visualization and evaluation of pathologic alterations in retinal structures due to ARMD.

Retinal topography and thickness mapping in atrophic age related macular degeneration

Aim: To determine the relation between alterations in the retinal topography and thickness, visual acuity, and retinal pigment epithelium hypopigmentation in atrophic age related macular degeneration (AMD). Methods: 22 patients, mean age 74 (SD 8) years, with atrophic AMD were recruited. An optical imaging system based on the retinal thickness analyser (RTA) was applied to generate a series of 20 optical section images that encompass 2 mm × 2 mm retinal areas. The optical section images were digitised and analysed to provide topographic maps of the vitreoretinal and chorioretinal surfaces and the retinal thickness. Vitreoretinal and chorioretinal surface elevations and retinal thickness were determined. Results: Variation in the vitreoretinal surface height was moderately correlated with visual acuity (r = −0.4; p = 0.03; n = 22). Increase in variation of chorioretinal surface height was correlated with decrease in visual acuity (r = −0.5; p = 0.01; n = 22). The retinal thickness was not associated with visual acuity (r = 0.2; p = 0.2; n=22). Relative height of the vitreoretinal surface in eyes with retinal pigment epithelium (RPE) hypopigmentation was significantly less than eyes without RPE hypopigmentation (p = 0.005). Eyes with and without RPE hypopigmentation had a similar relative height of the chorioretinal surface (p = 0.4). Retinal thickness in eyes with RPE hypopigmentation was less than in eyes without RPE hypopigmentation (p = 0.04). Conclusion: Mapping of chorioretinal and vitreoretinal topography and retinal thickness provides objective and quantitative measurements of retinal structural abnormalities and shows promise as an adjunct for the evaluation of retinal structural changes due to AMD.